1w76

ORTHORHOMBIC FORM OF TORPEDO CALIFORNICA ACETYLCHOLINESTERASE (ACHE) COMPLEXED WITH BIS-ACTING GALANTHAMINE DERIVATIVE
(see also 1W4L, 1W6R, and AChE bivalent inhibitors (Part II))

Biological Context
Alzheimer's disease is a disorder that attacks the central nervous system through progressive degeneration of its neurons. Patients with this disease develop dementia which becomes more severe as the disease progresses. It was suggested that symptoms of Alzheimer's disease are caused by a decrease in the activity of cholinergic neocortical and hippocampal neurons. Treatment for Alzheimer's disease by acetylcholine (ACh) precursors and cholinergic agonists was ineffective or caused side effects. The enzyme acetylcholinesterase (AChE) hydrolyses ACh, resulting in termination of cholinergic neurotransmission. Therefore, compounds which inhibit AChE might significantly increase the levels of ACh depleted by Alzheimer's disease. Galanthamine (1; GAL; Reminyl) is an AChE inhibitor and it is currently used for paliative therapy of Alzheimer's disease. The X-ray structure of Torpedo californica AChE (TcAChE) in complex with a bivalent galanthamine iminium derivative (4) was determined at 2.30 Å.



About this Structure
1W76 is a 2 chains structure of sequences from Torpedo californica. Full crystallographic information is available from OCA.

Additional Resources
For additional information, see: Alzheimer's Disease

Reference
Page seeded by OCA on Wed Feb 18 09:11:22 2009